The major objectives of this research project include correlation of the biochemical structure and physical-chemical characteristics of polypeptide hormones of the placenta and pituitary with their biologic and immunologic properties and an investigation of factors regulating the biosynthesis, storage and secretion of these hormones from normal and malignant endocrine cells. The project was initiated with a detailed analysis of the biochemistry of the hormone human placental lactogen (hPL), a protein hormone closely related to human pituitary growth hormone (hGH) and prolactin. In earlier work, we have established the amino acid sequence of hPL, identified its close homology with hGH and determined the structure of its biosynthetic precursor. We have identified smaller regions (1-134) of hPL and hGH which are responsible for their biologic activity and have examined modifications of the molecule by chemical and enzymic means, determining the effects on biologic, immunologic and physical-chemical properties. A disulfide-dimer of hPL which is not a precursor has been identified in the serum of pregnant women and in placental tissue at term. Its chemical structure has been determined. We plan to extend these studies to further modifications of the structure of the 1-134 region of hPL and hGH in trying to identify those features of structure which are responsible for the differences and similarities in the biologic activities of hPL and hGH. In physiologic studies using in vitro "perifusion" techniques, we plan to study the generation of the disulfide-dimer and to evaluate factors that may regulate production of hPL from normal tissue. Newer methodology using complementary DNA as a probe for normal and abnormal tissues will permit measurement of the concentrations of messenger RNA for hPL in normal tissue as well as in non-endocrine tumors that produce hPL or related peptides ("ectopic hormone production"). Choriocarcinoma cells in culture will be used as a model for in vitro regulation. These studies will provide further information on similarities and differences that exist in the biochemistry and physiology of placental and pituitary hormones. They will define further the structural basis of biologic activity and examine differences between production of the hormones in normal and malignant cells.